Category Archives: Induced Pluripotent Stem Cells

Induced Pluripotent Stem Cells

Induced Pluripotent Stem Cells and Hair Regeneration

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An excellent new study from Thailand just got published on May 30th in Frontiers in Cell and Developmental Biology. It examines the current status and advances in hair regeneration via induced pluripotent stem cells (iPSCs).

It also compares in detail hair regeneration via this method versus via follicular cell sources. I found this bifurcation very interesting.

I covered Thailand in past posts regarding doctors over there pioneering the use of oral Minoxidil for hair growth (20 plus years ago). Note that Thailand is also the world’s leader when it comes to gender reassignment surgery.

Induced Pluripotent Stem Cells Hair Growth
Human Induced Pluripotent Stem Cells (hiPSCs) and Hair Growth. Source: Front. Cell Dev. Biol., 30 May 2023.

Induced Pluripotent Stem Cells for Hair Regeneration

The two authors of this study are from the Siriraj Center for Regenerative Medicine and the faculty of medicine at Siriraj Hospital.

When it comes to hair follicle regeneration from human induced pluripotent stem cells (hiPSCs), the authors break it out into the following categories:

  1. Generation of individual hair follicle components. Further broken out into a) iPSC-derived trichogenic dermal cells. b) iPSC-derived folliculogenic epidermal cells. c) In vitro reconstruction of HFs with iPSC-derived dermal and epidermal cells.
  2. Generation of entire hair follicles from iPSCs. Further broken out into a) 3D integumentary organ system (IOS). b) Skin organoid.

When it comes to the 3D IOS method, they give the example of Dr. Takashi Tsuji and his RIKEN team’s success at generating a bioengineered 3D integumentary organ system (IOS) from mouse iPSCs (miPSCs). They also refer to studies by Ohyama and Tsuboi (lead researcher at Shiseido) that I have discussed in the past.

They also mention Dr. Koehler’s work that I covered in my post on hair-bearing human skin generated entirely from pluripotent stem cells. And of course they mention Stemson Therapeutics co-founder Dr. Terskikh and his past papers. When I interviewed the latter in 2017, he mentioned iPSCs in great detail.

Other subjects covered in the paper that I discussed in the past include biomimetic engineering of human hair and 3D culturing of hair cells.

Hair Follicle Regeneration from Follicular Cell Sources

The authors divide the follicular cell based hair regeneration methods into the following categories:

  1. Dermal papilla cells. Several decades ago, Aderans and Intercytex both saw some success in hair growth via dermal papilla cell culturing and injection into balding scalps. HairClone is currently trying something similar. And South Korea’s Epibiotech and Han Bio both seem to be rapidly progressing with this technology.
  2. Dermal sheath cup cells. This is what Shiseido is doing in Japan via the use and improvement of Replicel (Canada)’s technology.
  3. Hair follicle stem cells. The main disadvantage of this method with current culturing methods is rapid loss of stem cell abilities and spontaneous differentiation. Of interest, they mention a new March 2023 study from Fukuda et. al in relation to hair follicle stem cell expansion in hair regenerative medicine.

Make sure to also read my November 2022 post on effective cell therapy for hair regeneration. It was based on a very detailed new research paper authored by Epibiotech’s CEO.

Comparison of Cell Based vs hiPSC Based Methods

The below table from the new study is very useful. It compares the advantages and disadvantages of each method of hair regeneration.

The clear danger of the hiPSC method is potential tumorigenesis. Hence the reason why Stemson Therapeutics and OrganTech have to go through rigorous clinical trials. However, in return, iPSCs have the advantages of unlimited starting material, unlimited expansion and intrinsic hair-inductive ability.

iPSC versus cell based hair regeneration.
Comparison of iPSC versus hair follicle cell based hair regeneration. Source: Front. Cell Dev. Biol., 30 May 2023.

Conclusion

The paper makes the following statements towards the end that are of significance:

  • Autologous transplantation of dermal sheath cup cells (DSCs) is useful for patients with male and female pattern hair loss.
  • The generation of DSCs from hiPSCs may provide an unlimited source of cells for transplantation.
  • Nevertheless, bioengineered hair follicles are still required for some type of hair loss that involve entire hair follicles. Therefore, generating hair follicles through a biomimetic developmental approach is of interest.
  • Recent understanding of hair biology and iPSC technology offers hope for the generation of hair follicle components and entire hair follicles from hiPSCs.
  • Several approaches for reconstructing hair follicles from hiPSCs have been established. However, fully functional bioengineered hair follicles have yet to be developed.
  • Nevertheless, the authors conclude that these newer strategies for de novo folliculogenesis bring us one step closer to the ultimate goal.
Induced Pluripotent Stem Cells, RIKEN, Takashi Tsuji, Tokyo University of Science

Tokyo University and RIKEN Grow Skin with Hair Follicles

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On April 1, a distinguished team of researchers from Japan published an important paper in the journal Science Advances describing how they successfully grew skin tissue in the lab (using reprogrammed induced pluripotent stem cells) which was then transplanted onto mice.  The transplanted skin included fully functioning hair follicles with perfect growth and resting phase cycling (“no significant differences in the hair cycle periods were found between natural and bioengineered follicles“), sweat glands and sebaceous glands.  Note that the original cells were also taken from mice (from their gums to be precise).  Most importantly, there were no tumors or other life threatening disorders seen in the transplant recipient mice.  It is still too early to tell whether such skin can act as real skin when it comes to its function of protecting the human body, cooling it and so forth.

It seems like this team was led by Dr. Ryoji Takagi from Tokyo University of Science and the renowned Dr. Takashi Tsuji from RIKEN Center for Developmental Biology, with further collaboration with several other Japanese institutions.  On a somewhat related note, the main initial work surrounding induced pluripotent stem cells (known as iPS cells or iPSCs) was undertaken by Japanese scientist Dr. Shinya Yamanaka in 2006, and he was awarded the Nobel Prize for this in 2012.

When I first read this story I was planning to include it in my next brief items of interest post around the middle of this month.  I did not want to devote a whole blog post to this development (primarily because of the unclear human testing time frame projections involved — more on that later).  However, this discovery soon started getting widespread global coverage.  More importantly, 3 readers e-mailed me about it and probably another 10 posted about it in the comments to the last blog post!  All the main hair loss forums have threads on this subject too.  Here is some of the global coverage:

— BBC.

— Popular Mechanics.

— Daily Mail.

— Telegraph.

— Deutsche Welle.

— Mic.

— And from the horse’s own mouth.

The most debated issue on the hair loss forums has been the time frame before this is tested in humans. According to the BBC article “Researchers say this success will take 5-10 years to translate into humans.”  According to the Mic article, “Optimistically, Tsuji said, they’re looking at sometime in the next 10 years.”  According to the Popular Mechanics article, RIKEN researcher “Miho Ogawa estimates the first human trials will come within the next 10 years.”

I think that “within 10 years” could end up being in less than 5 years. I have three reasons for my optimism —

  1. Japan’s rapidly aging and declining population will need regenerative stem cell therapies well before most other countries in the world.
  2. As I have discussed on this blog many times in the past year or two, the Japanese government is nowadays extremely focused at speeding up human clinical trials in the regenerative medicine sector  that will allow for short cuts such as skipping stage 3 clinical trials.  I see no reason why they could also not speed up the process of moving from animal to human trials.
  3. When it comes to funding, Japan is a rich nation that can afford to spend substantially on such research.  Both via government funding and private funding (including foreign based private funding).  On a related not, in my last brief items of interest post from March, I discussed the recent collaboration between RIKEN and private sector company Meiji Seika related to hair loss (albeit it seems their might be some incorrect info in that announcement).  Also, in my second last brief items of interest post from February, I discussed another collaboration between RIKEN and Adjuvant Cosmetics.

Finally, it should be noted that more than for hair loss sufferers, this research is especially relevant to those with serious skin injuries and burns.  Moreover, these methods could one day be used to create functioning organs that are suitable for transplantation.  I recently read that once we have self-driving cars, traffic fatalities will decline to negligible levels, resulting in a major increase in already serious organ donor shortages.